The treatment recommendations of the National Asthma Education and Prevention Program (NAEPP) are based on disease severity. The four categories of disease severity are mild intermittent, mild persistent, moderate persistent and severe persistent asthma. The recommended therapies for severe persistent asthma include an anti-inflammatory agent (i.e., a high-dose inhaled corticosteroid), a long-acting bronchodilator (typically a beta₂ agonist) and oral corticosteroids. The leukotriene receptor antagonists are recommended as an alternative to inhaled corticosteroids in patients with mild to moderate persistent asthma, but experience with their use in patients with severe disease remains limited. Kemp and colleagues evaluated data on the efficacy of the leukotriene receptor antagonist zafirlukast in patients with severe persistent asthma.

The authors analyzed pooled data from four randomized, double-blind, placebo-controlled trials of zafirlukast in patients with asthma. These patients had never received corticosteroids. The authors identified a subset of 261 patients who at the time of the clinical trials were classified as having mild to moderate asthma (forced expiratory volume in one second [FEV₁] of less than 60 percent of the predicted value). However, since those four studies were conducted, the NAEPP classification of disease severity changed. With the current classification system, patients such as these, with an FEV₁ of less than 60 percent of predicted, are considered to have severe persistent asthma.

All of the 261 patients had an FEV₁ of less than 60 percent of predicted but an increase of at least 15 percent in the FEV₁ after inhalation of a bronchodilator. Each of the four studies lasted 13 weeks and were of a similar design. The treated patients received 20 mg of zafirlukast twice daily. The use of a beta agonist was allowed on an as-needed basis. During the initial screening and treatment, patients kept a record of their daily peak expiratory flow rates, asthma symptom scores and beta agonist use. At the beginning of the studies, the average FEV₁ was 53 percent of predicted, the mean number of puffs per day of a beta agonist was six, and patients experienced four to five asthma-related nighttime awakenings per week.

Pooled data revealed that 64 percent of the patients who used zafirlukast had a 10 percent or greater increase in FEV₁, compared with 50 percent of the patients in the placebo group. In addition, pulmonary function deterioration occurred in 21 percent of the patients in the zafirlukast group but in 35 percent of the patients in the placebo group. More importantly, the treatment group had a 26 percent decrease in daytime asthma symptom scores, a 27 percent decrease in nighttime awakenings, a 24 percent decrease in mornings with asthma symptoms and a 26 percent decrease in the use of a beta agonist. In addition, among patients with daily peak flow variability of more than 20 percent, the zafirlukast group had significant increases in both morning and evening peak expiratory flow rates compared with the placebo group.

The authors conclude that zafirlukast offers significant benefit, even as monotherapy, in patients with severe persistent asthma. Because the number and severity of adverse events did not differ in the treatment and placebo groups, this leukotriene receptor antagonist also appears to be a safe therapy. Additional studies are needed to evaluate this class of medication for use in combination with inhaled corticosteroids or other anti-inflammatory agents.